This invention relates to 3-substituted 2,4,6-trihalogenated benzamides and their use as sweetening agents.
The so-called synthetically produced "sweeteners" with a far higher sweetening effect than cane sugar (sucrose) have been known for a long time. The most well-known representatives of this class of substances are saccharin, Dulcin, and sodium cyclamate, as well as "Aspartame" and 2-amino-4-nitro-1-phenyl-n-propyl ether ("Ultrasuss", P 4000).
Synthetic sweeteners should exhibit, besides a high degree of sweetening (low-load compound), no side effects and a very high compatibility. Furthermore, they must be able to withstand without changes the thermal stresses during the cooking or baking process. A lack of heat stability, for example, limits the range of applications of "Aspartame" to a great extent; and the objections from a health viewpoint existing against Dulcin resulted in prohibition of the use of Dulcin, for example, in the Federal Republic of Germany and in the United States of America.
Compounds of formula I wherein Hal is iodine and Z is the group ##STR3## wherein P is 1 and K, L, M are 0;
N is 0; PA1 Y is --CH.sub.3, --C.sub.2 H.sub.5, --C.sub.4 H.sub.9, --Phenyl; or PA1 N is 1 or 2; PA1 X and Y are a hydrogen atom and salts thereof with bases are disclosed in the DAS 1 568 959. They are disclosed to be suitable for use as opacifiers in cholecystography and as choleretics. PA1 Z is a carboxyl group, or represents the group ##STR5## wherein P and L are each independently 0 or 1, with the proviso that L is 0 when either P or K is 0; PA1 K is 0, 2, 3 or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 0 or 1; PA1 X is a hydrogen atom; PA1 Y is a hydrogen atom or a lower alkyl group of 1-4 carbon atoms or, when either M or N is other than 0, an optionally etherified or esterified hydroxy group, or when N is 1 and M is other than 0, X and Y together form an additional carbon-carbon bond; or wherein PA1 (B) Hal is an iodine atom; and PA1 Z is a carboxyl group, or represents the group ##STR6## wherein (1) P and L are each 0; PA1 K is 0, 2, 3 or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 0 or 1; PA1 X is a hydrogen atom; PA1 Y is a hydrogen atom, a lower alkyl group of 1-4 carbon atoms, or an optionally etherified or esterified hydroxy group, or when N is 1 and M is other than 0, X and Y together form an additional carbon-carbon bond; or PA1 (2) P and L are each 1; PA1 K is 2, 3 or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 0 or 1; PA1 X is a hydrogen atom; and PA1 Y is a hydrogen atom or a lower alkyl group of 1-4 carbon atoms; or PA1 (3) P is 1; PA1 L is 0; PA1 K, M and N are each 0; and PA1 Y is a hydrogen atom; or PA1 (4) P is 1; PA1 L is 0; PA1 K is 0; PA1 M is 1 or 2; PA1 N is 0; and PA1 Y is a lower alkyl residue of 1-4 carbon atoms; or PA1 (5) P is 1; PA1 L is 0; PA1 K is 2, 3, or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 1; PA1 X is a hydrogen atom; and PA1 Y is a hydrogen atom or a lower alkyl residue of 1-4 carbon atoms; PA1 Z is a carboxyl group or the group ##STR8## wherein P is 1 and L is 0 or 1 with the proviso that L is 0 when K is 0; PA1 K is 0, 2, 3 or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 0 or 1; PA1 X is a hydrogen atom; PA1 Y is a hydrogen atom or a lower alkyl group of 1-4 carbon atoms, or when either M or N is other than 0, a hydroxy group, a C.sub.1-6 alkoxy group or a C.sub.1-4 acyloxy group; or, when N is 1 and M is other than 0, X and Y together represent an an additional carbon-carbon bond; or PA1 P and L are 0 PA1 K is 0, 2, 3 or 4; PA1 M is 0, 1, 2 or 3; PA1 N is 0 or 1; PA1 X is a hydrogen atom, PA1 Y is a hydrogen atom, a lower alkyl group of 1-4 carbon atoms, a hydroxy group, a C.sub.1-6 alkoxy group, a C.sub.1-4 acyloxy group or, when N is 1, X and Y together represent an additional carbon-carbon bond; PA1 Z' is the group --COOH, --COOR.sup.1, or ##STR12## wherein R.sup.1 is a hydrogen atom or a lower alkyl residue of 1-4 carbon atoms, and P, K, L, M, N, X and Y are as defined above for formula I, is partially hydrolyzed to the benzamide conventionally by reaction with an alkali; or PA1 R.sup.1 is a lower alkyl residue of 1-4 carbon atoms, and PA1 K, L, M, N, X and Y are as defined for formula I(A); or PA1 Z' is either --COOH or the group ##STR18## and P and L are 0.
The need is great for artificial sweeteners having a stronger degree of sweetening and a further improved general compatibility, both for medical reasons (diabetics) and for dietetic reasons (reduction of calories).